Different stapling-based peptide drug design: Mimicking α-helix as inhibitors of protein–protein interaction

Abstract Peptide stapling strategy has been proven a promising solution in addressing two major pharmacological hurdles, proteolytic stability and membrane permeability, for small peptides as therapeutics. This stapling peptides feature a covalent cross-link of side chains, thus effectively mimicking α-helix as inhibitors of protein–protein interactions. In this review, we category and analyze key examples of various peptide stapling strategies based on different cross-links aligned on the side chain of peptides mainly in the last three years.